Epilepsy is a common neurological disorder that is characterized by recurrent, spontaneous seizures. Epilepsy is a major public health issue with inadequate treatment options. Over 70 million people worldwide have epilepsy. This is more than cerebral palsy, multiple sclerosis, and Parkinson?s disease combined. Although more than two-dozen antiseizure drugs (ASDs) exist, approximately one-third of patients (over 20 million) suffer from uncontrollable seizures, i.e. drug-resistant epilepsy. Despite the advent of various new ASDs over the past 30 years, the incidence of refractory epilepsy has not changed. One potential explanation for this disappointing fact is that ASD screening continues to utilize the same conventional methods. In fact, ASD screening has not appreciably evolved since the first study in 1938. The continued use of conventional methods?in other words, maintenance of the status quo?is unlikely to identify better substances. A new approach is needed. In a recent pilot experiment, we at Expesicor achieved proof-of-concept that a novel approach, called the KaL method, can reliably reproduce fundamental characteristics of refractory human epilepsy. The main goal of the proposed project is to develop and commercialize two animal models based on the KaL method that (1) reliably recapitulate fundamental aspects of the epilepsy phenotype and (2) exhibit seizures that are refractory to ASDs. Our team is comprised of experts in various areas of epilepsy R&D, ranging from preclinical studies to clinical trials. We also have substantial experience in biotechnology commercialization. If successful, this project will lead directly to the implementation of the KaL method in drug discovery/screening efforts for new and better ASDs. Our target customers are owners of substances with potential antiseizure effects. This ranges from small biotech firms to the largest pharmaceutical companies. To emphasize the need for novel drug screening approaches and to demonstrate existing demand for our services, we have secured letters of intent from four potential customers. The KaL method directly challenges the existing drug screening paradigm, which has failed to reduce the incidence of refractory epilepsy. This project has the potential to revolutionize the current ASD screening paradigm, which is long overdue for a breakthrough.